face

13 John McDougal’s article, “The Paleo Diet Is

Uncivilized (And Unhealthy and Untrue)”
By Alan Aragon

16 Carbohydrate is protein-sparing... What exactly

does that mean?
By Alan Aragon

Copyright © June 1st, 2012 by Alan Aragon

Home: www.alanaragon.com/researchreview
Correspondence: aarrsupport@gmail.com

2 Issues with assumptions made by angels in the

ivory tower.
By Alan Aragon

5 Consumption of fructose- but not glucose-

sweetened beverages for 10 weeks increases
circulating concentrations of uric acid, retinol
binding protein- 4, and gamma-glutamyl
transferase activity in overweight/obese humans.
Cox CL, et al. Nutr Metab (Lond). 2012 Jul 24;9(1):68.
[Epub ahead of print] [Pubmed]
6 Whey protein before and during resistance
exercise has no effect on muscle mass and
strength in untrained young adults.
Weisgarber KD, et al. Int J Sport Nutr Exerc Metab. 2012
Jul 4. [Epub ahead of print] [Pubmed]
7 The effects of four hypocaloric diets containing
different levels of sucrose or high fructose corn
syrup on weight loss and related parameters.
Lowndes J, et al. Nutr J. 2012 Aug 6;11(1):55. [Epub ahead
of print] [Pubmed]

8 Aspartame in conjunction with carbohydrate

reduces insulin levels during endurance exercise.
Siegler J, et al. J Int Soc Sports Nutr. 2012 Aug 1;9(1):36.
[Epub ahead of print] [Pubmed]

10 The impact of metabolic stress on hormonal

responses and muscular adaptations.
Goto K, et al. Med Sci Sports Exerc. 2005 Jun;37(6):955-
63. [Pubmed]
Alan Aragon’s Research Review – June 2012 [Back to Contents] Page 1

Issues with assumptions made by angels in the ivory
tower.
By Alan Aragon
_________________________________________________________________
Intro to infallibility
This article is an off-shoot of the previous issue's discussion
about protein frequency, but this time, I'll focus more on the so-
called postexercise anabolic window. Before I dive into it, let me
explain the title I chose. For those unfamiliar, the term ivory
tower has biblical origins, where it was used to describe noble
purity. In current times, the term is more commonly used to
describe the academic elite. Occasionally, those in the ivory
tower acknowledge their perceived status. A good example of
this is a review by Tipton & Witard1 titled, "Protein
requirements and recommendations for athletes: relevance of
ivory tower arguments for practical recommendations." These
authors implicitly conveyed the idea that there can often be a
frustrating disconnect between the esoteric musings of scientists
in the lab and the practical traditions carried out in the real
world.
A related concept to the ivory tower is a cognitive bias that
psychologist Edward Thorndike called the constant error of the
halo, 2 which most currently refer to as the halo effect. This term
describes the tendency to falsely assume that one favorable trait
in a given person automatically means that his other traits or
capabilities are favorable as well. The halo effect is apparent in
the way many people view the opinions of researchers at the top
of their fields as unquestionably correct. This perceived
infallibility is the source of constant appeals to authority when
justifying this protocol or that. A standout halo-bearer to whom
constant appeals and references are made is Stuart Phillips (bio
here), who is one of the top researchers in areas related to
skeletal muscle metabolism. Many of the academically inclined
folks in the fitness and sports nutrition circles see his opinions
on protein-related issues as the final word. However, I feel that a
couple of Phillips' cornerstone claims are not strongly supported
enough to warrant the degree of confidence I've seen in them.
Let's get into this.
Windows of opportunity
I used to think that the enamorment with the postexercise
"anabolic window of opportunity" was exclusive to bodybuilders
and wannabe bodybuilders susceptible to fitness-related hype
and lore. For the one or two of you who are unaware of this
concept, the so-called anabolic window is a short period after the
resistance training bout where immediate nutrient dosing is
presumed to enhance muscle recovery and growth. The heralded
tactic is to jump at this window of opportunity by having fast-
absorbing protein and carbohydrate as soon as possible
postexercise. As many of you are aware, this recommendation is
largely based on short-term studies in overnight-fasted subjects,
rendering it subject to more solid confirmation by chronic
studies involving sound overall macronutrition. So, seeing
Phillips espouse the same old lore took me aback. In a recent
Alan Aragon’s Research Review – June 2012
review (which I'll repeatedly refer to), Phillips & Van Loon
mused over what might be the optimal time for protein dosing
relative to the resistance training bout.3 They stated that while
studies on postexercise protein and/or amino acid dosing show
unequivocally positive effects on muscle anabolism, it's
impossible to know whether pre-exercise dosing is beneficial for
stimulating muscle protein synthesis (MPS) since the data in this
area is mixed. Illustrating this, they cite 3 studies total, the first
of which is Tipton et al's research showing that 6 g of essential
amino acids (EAA) plus 30 g sucrose (CHO) ingested
immediately pre-exercise caused greater MPS than the same
solution ingested immediately postexercise.4
To illustrate the non-effect of pre-exercise dosing, they cited two
studies, but one of them had notable limitations, and the other
simply did not support their point. First up, Fujita et al did not
observe greater postexercise MPS from ingesting pre-exercise
EAA + CHO compared to training fasted.5 However, it's
important to note that although the pre-exercise EAA dose
(~18.3 g EAA + 26.2 g CHO) was greater than Tipton et al's, it
was ingested an hour before training, as opposed to immediately
before training, which in Tipton et al's case, caused higher
insulin elevations during training – potentially explaining the
greater amino acid delivery to muscle. Phillips & Van Loon cite
another study by Tipton et al to illustrate the non-effect of pre-
exercise protein dosing on MPS.6 To quote Phillips & Van Loon
(I bolded the critical part):3
"With respect to resistance exercise, some studies have
shown that pre-exercise protein consumption can enhance
MPS (Tipton et al., 2001) and others have shown no effect
(Fujita et al., 2009; Tipton et al., 2006). Thus, at this time
pre-exercise feeding appears unlikely to increase MPS and
long-term gains in muscle mass."
But as I mentioned, this study simply does not support their
intention to cite research showing no MPS from pre-exercise
protein dosing. A 20 g dose of whey taken immediately pre-
exercise was equally as effective at stimulating MPS as the same
dose ingested 1 hour postexercise. Specifically, in the pre-
exercise dosing condition, amino acid delivery to the leg was
elevated to 4.4 times pre-exercise resting levels during exercise,
and returned to baseline levels at 3 hours postexercise. In the
post-exercise dosing condition, amino acid delivery to the leg
was 2.1 times resting levels at 2 hours postexercise, and
remained at roughly 1.7 times resting levels for the remainder of
the 5-hour postexercise test period. To quote Tipton et al:6
"Unlike the response to EAA in our previous study, the
anabolic response to whey protein ingestion was similar
whether ingested before or following exercise. Thus it seems
that muscle protein accretion is stimulated by ingestion of
whey proteins, and the timing of the ingestion in relation to
the exercise is not as important for this response as it was for
EAA."
So, it appears that although effects of intact proteins (as opposed
to free-form/isolated amino acids) are less influenced by pre- vs.
postexercise timing, their anabolic effect exists nonetheless -- at
least in the short-term. For those favoring simplicity, a practical
application of this finding would be to have a substantial dose of
intact protein (such as whey) pre-exercise. This would lend
[Back to Contents] Page 2
flexibility to the timing of the postexercise meal, since its
urgency would be virtually nullified. Having a large pre-exercise
protein dose would mimick the action of protein consumed
immediately postexercise (during the "magical" anabolic
window). I'll quote Phillips et al's practical recommendation,3
then support my previous point further:
"While there is some debate about the ‘‘critical’’ nature of
the timing of postexercise protein consumption, a simple
message may be that the earlier after exercise an athlete
consumes protein the better."
With so much focus on the postexercise period and getting
protein down the hatch as quickly as possible, it boggles my
mind that the simple act of having intact protein pre-exercise to
meet immediate postexercise needs is overlooked (or in Phillips
et al's case, dismissed). People easily forget recent research by
Power et al,7 which showed that a 45 g dose of whey isolate
caused insulin levels to peak at roughly 40 minutes after
ingestion, and remain elevated above levels known to max-out
the anabolic response (15‐30 mU/L, or 104‐208 pmol/L8) for
about 2 hours. And keep in mind, the addition of carbohydrate to
this dose of whey would push the insulin peak higher and draw
its elevation out for a longer period. Blood amino acid levels
peaked at roughly 50-60 minutes after ingestion, and didn't
return close to baseline levels until the end of the 3-hour testing
period. Have a look for yourself – and note that my commentary
has been on whey isolate, but whey hydrolysate's effects are also
illustrated below:
Alan Aragon’s Research Review – June 2012
Hasty extrapolation of acute effects
Phillips & Van Loon seem confident that acute (short-term)
effects of protein timing relative to resistance training on MPS
translate to greater strength &/or size adaptations over the long-
term, which is evident in the following quote:3
"So while a crucial ‘‘window of anabolic opportunity’’ is
not, at least currently, well defined, it would make sense that
protein provision should begin as soon as possible after
exercise to promote recovery and possibly to enhance the
rate of – or absolute level of – adaptation"
While this line of speculation is not illogical or implausible
given the short-term data, there always seems to be an omission
of chronic (non-acute/longer-term) research showing no effect of
timing. Burk et al's study9 comparing time-focused & time-
divided protein doses (and finding no difference) is briefly
alluded to, but it's not in the specific context of chronic studies
failing to show timing effects. Another null-effect chronic study
missing from discussion in Phillips & Van Loon's review is by
Hoffman et al, who failed to detect a differential effect of protein
supplementation closely sandwiching the training bout compared
to positioning it away from the bout.10 Importantly, the latter two
studies can't be pegged for using marginal protein doses such as
yet another null-effect chronic timing trial by Wycherly et al,
which used 21 g protein doses.11 In contrast, Burk et al &
Hoffman et al respectively used 35 g & 42 g doses of high-
quality protein. With the exception of the elderly,12 both of those
doses are likely to meet or exceed thresholds known to max-out
acute MPS.13,14 And still, they didn't cause timing-mediated
differences in muscular adaptations over a chronic period.
Concluding thoughts
Although the study of nutrient dosing relative to resistance
training has been done since what seems to be the beginning of
time, there's no landslide of data indicating the superiority of a
particular protocol. The issues I raised in this discussion are just
a drop in the bucket of lingering uncertainties, which too often
are assumed to be sure bets. The closest we have come to an
indisputable guideline is that hitting the total daily protein target
for the given goal should take top priority over the timing of its
constituent doses. Once that's established, the secondary
concerns such as timing & distribution can be messed with in
attempt to optimize adaptations. Absolutes beyond this are not
likely to exist – despite regular sightings of angels with halos.
References
1. Tipton KD, Witard OC. Protein requirements and
recommendations for athletes: relevance of ivory tower
arguments for practical recommendations. Clin Sports Med.
2007 Jan;26(1):17-36. [Pubmed]
2. Thorndike EL. A constant error in psychological ratings. J
Appl Psychol. 1920 Mar;4(1):25-9. [Summary in PDF]
3. Phillips SM, Van Loon LJ. Dietary protein for athletes:
from requirements to optimum adaptation. J Sports Sci.
2011;29 Suppl 1:S29-38. [Pubmed]
4. Tipton KD, et al. Timing of amino acid-carbohydrate
ingestion alters anabolic response of muscle to resistance
exercise. Am J Physiol Endocrinol Metab. 2001
Aug;281(2):E197-206. [Pubmed]
[Back to Contents] Page 3
5. Fujita S, et al. Essential amino acid and carbohydrate
ingestion before resistance exercise does not enhance
postexercise muscle protein synthesis. Appl Physiol. 2009
May;106(5):1730-9. Epub 2008 Jun 5. [Pubmed]
6. Tipton KD, et al. Stimulation of net muscle protein
synthesis by whey protein ingestion before and after
exercise. Am J Physiol Endocrinol Metab. 2007
Jan;292(1):E71-6. [Pubmed]
7. Power O, et al. Human insulinotropic response to oral
ingestion of native and hydrolysed whey protein. Amino
Acids. 2009 Jul;37(2):333-9. Epub 2008 Aug 5. [Pubmed]
8. Greenhaff PL, et al. Disassociation between the effects of
amino acids and insulin on signaling, ubiquitin ligases, and
protein turnover in human muscle. Am J Physiol Endocrinol
Metab. 2008 Sep;295(3):E595-604. [Pubmed]
9. Burk A, et al. Time-divided ingestion pattern of casein-
based protein supplement stimulates an increase in fat-free
body mass during resistance training in young untrained
men. Nutr Res. 2009 Jun;29(6):405-13. [Pubmed]
10. Hoffman JR, et al. Effect of protein-supplement timing on
strength, power, and body-composition changes in
resistance-trained men. Int J Sport Nutr Exerc Metab. 2009
Apr;19(2):172-85. [Pubmed]
11. Wycherley TP, et al. Timing of protein ingestion relative to
resistance exercise training does not influence body
composition, energy expenditure, glycaemic control or
cardiometabolic risk factors in a hypocaloric, high protein
diet in patients with type 2 diabetes. Diabetes Obes Metab.
2010 Dec;12(12):1097-105. [Pubmed]
12. Yang Y, et al. Resistance exercise enhances myofibrillar
protein synthesis with graded intakes of whey protein in
older men. Br J Nutr. 2012 Feb 7:1-9. [Epub ahead of print]
[Pubmed]
13. Moore DR, et al. Ingested protein dose response of muscle
and albumin protein synthesis after resistance exercise in
young men. Am J Clin Nutr. 2009 Jan;89(1):161-8.
14. Koopman, et al. Coingestion of carbohydrate with protein
does not further augment post-exercise muscle protein
synthesis. Am J Physiol Endocrinol Metab. 2007
Sep;293(3):E833-42. [Pubmed]

Alan Aragon’s Research Review – June 2012 [Back to Contents] Page 4


Consumption of fructose- but not glucose-sweetened
beverages for 10 weeks increases circulating
concentrations of uric acid, retinol binding protein- 4,
and gamma-glutamyl transferase activity in
overweight/obese humans.
Cox CL, et al. Nutr Metab (Lond). 2012 Jul 24;9(1):68. [Epub
ahead of print] [Pubmed]
BACKGROUND: Prospective studies in humans examining the
effects of fructose consumption on biological markers associated
with the development of metabolic syndrome are lacking. Therefore
we investigated the relative effects of 10 wks of fructose or glucose
consumption on plasma uric acid and RBP-4 concentrations, as well
as liver enzyme (AST, ALT, and GGT) activities in men and
women. METHODS: As part of a parallel arm study, older (age 40-
72), overweight and obese male and female subjects (BMI 25-35
kg/m2) consumed glucose- or fructose-sweetened beverages
providing 25% of energy requirements for 10 wks. Fasting and 24-h
blood collections were performed at baseline and following 10 wks
of intervention and plasma concentrations of uric acid, RBP-4 and
liver enzyme activities were measured. RESULTS: These findings
suggest that consumption of fructose at 25% of energy requirements
for 10 wks, compared with isocaloric consumption of glucose, may
contribute to the development of components of the metabolic
syndrome by increasing circulating uric acid, GGT activity,
suggesting alteration of hepatic function, and the production of
RBP-4. CONCLUSIONS: These findings suggest that consumption
of fructose at 25% of energy requirements for 10 wks, compared
with isocaloric consumption of glucose, may contribute to the
development of components of the metabolic syndrome by
increasing circulating uric acid, GGT activity, suggesting alteration
of hepatic function, and the production of RBP-4.
SPONSORSHIP: This research was supported with funding from
NIH grant RO1 HL-075675, & also from Grant #UL1 RR024146
from the National Center for Research Resources (NCRR), a
component of the NIH, and NIH Roadmap for Medical Research.
Study strengths
Although the phases were short, this study consisted of both an
in-patient intervention period (subjects lived at the lab for 2
weeks), followed by an outpatient intervention period, ending
with another 2-week in-patient period. During the first in-patient
period, subjects consumed a diet whose carbohydrate was
primarily starch, while the final in-patient reflected the prior 8
weeks, where 25% of total energy was from either fructose or
glucose-sweetened beverages. An advantage to this setup is that
it examines the effects of both lab conditions and real-world
conditions. This study is innovative because it's the first to ever
measure the effects of excessive sugar intake on 24-hour uric
acid levels, GGT activity, and RBP-4 levels in humans, all of
which may play impotant roles in the metabolic syndrome.
Study limitations
The authors acknowledge one limitation - a small number of
subjects (16 men, 16 women). I would also add that the in-
patient phase should have been at least as long as the out-patient
phase, since the latter is subject to a lack of control & thus a high
degree of confounding variability. Furthermore, the
macronutrient breakdown of the 10-week intervention period
was (15% protein, 55% carbohydrate, 30% fat), which is very
Alan Aragon’s Research Review – June 2012
close to the proportions in the standard Western diet. This spells
limited relevance to other populations, particularly health &
fitness-oriented populations who typically consume far less
carbohydrate - both in an absolute and proportional sense -
especially in dieting scenarios. It's tough to imagine a scenarios
where it's appropriate to put overweight & obese people on a
low-protein/high-carbohydrate diet. Total carbohydrates
consumed was approximately 300 g, which indeed might be
reflective of what obese/sedentary individuals consume as part
of what maintains them. However, it would be very dicey to
assume that the outcomes of this study apply to other
populations (particularly athletic/active folks & dieters).
Another limitation of this study's design was that the beverages
were specially designed to be sweetened by either glucose or
fructose. Glucose-only & fructose-only beverages are rare to
nonexistent in the commercial food supply. One of the only big-
selling beverages I can think of that's sweetened exclusively with
fructose is Vitamin Water, which contains slightly over 30 g
fructose per 591 ml bottle. Vitamin Water came under fire last
year from the UK's independent-yet-influential Advertising
Standards Authority (ASA), which ruled that the product's claim
to be nutritious (due to its vitamin content) was misleading due
to its sugar content. Almost every other commercially available
sugar-sweetened beverage has a nearly even mix of glucose &
fructose, by virtue of being sweetened by sucrose or HFCS
(which is functionally equivalent to sucrose).
This brings us to the amount of fructose and glucose consumed
during the 10-week comparison phase. At 25% of total kcals the
subjects consumed, this amounts to roughly 150 g fructose or
glucose, which in real-world terms, would require the
consumption of about 7 cans of non-diet soda. Anyone who
consumes 7 cans of non-diet soda per day has problems that span
far beyond fructose. The authors cite a 2008 Economic Research
Survey (ERS) bulletin indicating that added sugar comprises
24% of total energy.1 However, the most recent ERS data
(updated July, 2012) shows that caloric sweeteners comprise
16.9% of total energy.2 In terms of a concrete number, Vos et al
reported that the average consumption of fructose by children
and adults in the US is 54.7 g/day, which equates to 10.2% of
total intake (putting mean sugar intake at roughly 20.4%, since
fructose is only half of what comprises most added sugars).3
This begs the question of why the authors of the present study
used nearly triple the average fructose consumption as a test
dose, when it's painfully obvious that any isolated nutrient in
gross excess can cause a range of health problems.
Comment/application
This study added to previous findings by showing that a rather
huge amount of fructose (appx 150 g/day) elevates 24-hour uric
acid levels , the liver enzyme GGT, and RBP-4 (associated with
increased visceral adiposity & decreased insulin sensitivity).
These changes can collectively contribute to the metabolic
syndrome in overweight & obese individuals. The practical
application here is for sedentary folks to keep fructose from
added sugars to a maximum of roughly 50 g/day, or about a third
of the dose used in this study. The other practical
recommendation is to refer back to a well-done review by
Rizkalla,4 who concluded that moderate fructose consumption
(roughly 10% of total calories; at or below 50 g/day) "...appears
acceptable and potentially beneficial."
[Back to Contents] Page 5
Whey protein before and during resistance exercise
has no effect on muscle mass and strength in
untrained young adults.
Weisgarber KD, et al. Int J Sport Nutr Exerc Metab. 2012 Jul 4.
[Epub ahead of print] [Pubmed]
PURPOSE: To determine the effects of whey protein before and
during resistance exercise (RE) on body composition and strength in
young adults. METHODS: Participants were randomized to ingest
whey protein (PRO; 0.3g·kg-1 protein; n=9, 24.58±1.8 yrs,
88.3±17.1 kg, 172.5±8.0 cm) or placebo (PLA; 0.2g·kg-1 corn-
starch maltodextrin + 0.1g·kg-1 sucrose; n=8, 23.6±4.4 yrs,
82.6±16.1 kg, 169.4±9.2 cm) during RE (3 sets of 6-10 repetitions
for 9 whole-body exercises), which was performed 4 days per week
for 8 weeks. Protein and placebo were mixed with water (600ml)
and 50% of the solution containing 0.15g·kg-1 of protein or placebo
was consumed immediately prior to the start of exercise and ~1.9%
of the remaining solution containing ~0.006g·kg-1 of protein or
placebo was consumed immediately following each training set.
Before and after the study, measures were taken for lean tissue mass
(D), muscle size of the elbow and knee flexors and extensors and
ankle dorsi flexors and plantar flexors (ultrasound), and muscle
strength (1-repetition maximum chest press). RESULTS: There
was a significant increase (p<0.05) in muscle size of the knee
extensors (PRO: 0.6±0.4 cm, PLA: 0.1±0.5 cm), knee flexors (PRO:
0.4±0.6 cm, PLA: 0.5±0.7 cm), ankle plantar flexors (PRO: 0.6±0.7
cm, PLA: 0.8±1.4 cm), and chest press strength (PRO: 16.6±11.1
kg, PLA: 9.1±14.6 kg) over time, with no differences between
groups. CONCLUSIONS: The ingestion of whey protein
immediately before the start of exercise and again following each
training set has no effect on muscle mass and strength in untrained
young adults. SPONSORSHIP: None listed.
Study strengths
This study is innovative since it's the first to test the effects of
whey protein before and during training - unlike previous
research by Belen et al, which used an expensive, proprietary,
enzymatically altered casein hydrolysate called PeptoPro®.5
Body composition was assessed via dual x-ray absorptiometry
(DXA), and muscle thickness was assessed via ultrasound. In
addition, 1-repetition maximum (1RM) was also assessed, which
puts this study among the minority that have measured
nutritional effects on body composition, muscle morphology, &
exercise performance - as opposed to merely short-term effects.
Study limitations
The authors responsibly acknowledge a few limitations. The 8-
week trial duration may not be sufficient to detect small changes
that could potentially be seen with a longer trial and a larger
number of subjects (as opposed to only 8 in the protein
condition, and 8 in the control condition). The authors further
nit-picked at the limitations of their instruments. Perhaps nit-
pickingly, they mentioned that DXA's assessment of lean mass
also includes other areas of the body than the trained muscles,
which can confound the specificity of effects between muscle
groups, and ultrasound does not differentiate between contractile
& non-contractile tissue - therefore, a more advanced method
such as magnetic resonance imaging (MRI) might give a more
accurate set of results. I would add that although dietary intake
was tracked & analyzed, it was not reported in the manuscript.
This omission of data is potentially profound since the
macronutrient composition of the diet can have a strong
influence on net gains in muscle over time. Since the subjects'
Alan Aragon’s Research Review – June 2012
bodyweight did not change over the course of the trial, it's
possible that a sufficient total daily protein intake
(approximately 1.2g/kg or more) overrode any significant
supplemental protein effects.
The authors chose untrained subjects in order to maximize the
response to the protocol. I would contend that this could also be
confounding, since the greater response of untrained subjects
could have overrode the supplemental effects. If trained athletes
were used, the detection of any significant effects would be more
meaningful. The trained/athletic population is closer to its
potential for both muscle size and performance (thus the greater
practicality of "seeking the edge" in advanced trainees). Another
potential limitation was the training protocol. Despite its
progressive nature, it was whole-body, 4 times per week (9
exercises, 3 sets each). This frequency of sessions strikes me as
odd, and not just because it's rarely done in the real-world
among trainees whose primary goals are muscular hypertrophy
& strength. Peterson et al examined the results of 2 meta-
analyses, which collectively determined that for untrained
subjects, maximal strength gains are achieved by a training
frequency of 3 times per week.6 The latter research is consistent
with what I've seen in the field with novice trainees.
Comment/application
The lack of effects seen in the present study are open to
speculation in the midst of missing data - the largest of which
was macronutrient intake. However, there are a few
worthwhile/educated guesses that can be made. Assuming that
total protein intake was not an influencing factor (as unlikely as
it may be), an alternate explanation is that the whey dosing
scheme was insufficient to yield special effects. As mentioned
by the authors, previous research of similar design by Belen et al
showing positive effects dosed protein in larger boluses.5
Specifically, the present study involved a pre-workout dose of
0.15 g/kg (13.24 g), followed by 0.006 g/kg (0.52 g) after each
set. In contrast, Belen et al administered their protein doses
every 15 minutes during exercise, equaling the same total
protein dose of the present study by the end of the training bout,
but larger constituent doses. Furthermore, Belen et al's protein
dose was co-ingested with an equal amount of carbohydrate,
whereas the present study tested protein-only against a
carbohydrate-only control. This combination of protein &
carbohydrate could have factored into the positive results seen.
However, the pre- & during-exercise combined protein dose of
the present study (0.3 g/kg) amounted to roughly 26.5 g. This is
an important detail because Staples et al recently showed that a
postexercise dose of 50 g maltodextrin co-ingested with 25 g
whey had no further anabolic effect - at least in the short term -
compared to 25 g whey alone.7
It's important to note that although the differences in the present
study lacked statistical significance, they existed nonetheless.
Protein supplementation increased the amount of work
performed for 5 out of the 9 exercises. It also increased the size
of the knee extensors, knee flexors, & ankle plantar flexors. But
for all we know, this could merely be a result of the added total
protein to the diet, as opposed to the dosing pattern of the protein
relative to the training bout. A more worthwhile comparison
would be a substantial pre- or post-workout bolus of protein (25-
40 g) compared to the same dose spread in even doses
throughout the training bout. Of course, matching total daily
protein intake would allow the assessment of timing effects.
[Back to Contents] Page 6
The effects of four hypocaloric diets containing
different levels of sucrose or high fructose corn syrup
on weight loss and related parameters.
Lowndes J, et al. Nutr J. 2012 Aug 6;11(1):55. [Epub ahead of
print] [Pubmed]
BACKGROUND: The replacement of sucrose with HFCS in
food products has been suggested as playing a role in the
development of obesity as a public health issue. The objective of
this study was to examine the effects of four equally hypocaloric
diets containing different levels of sucrose or high fructose corn
syrup (HFCS). METHODS: This was a randomized,
prospective, double blind trial, with overweight/obese
participants measured for body composition and blood chemistry
before and after the completion of 12 weeks following a
hypocaloric diet. The average caloric deficit achieved on the
hypocaloric diets was 309 kcal. RESULTS: Reductions were
observed in all measures of adiposity including body mass, BMI,
% body fat, waist circumference and fat mass for all four
hypocaloric groups, as well as reductions in exercise only group
for body mass, BMI and waist circumference.
CONCLUSIONS: Similar decreases in weight and indices of
adiposity are observed when overweight or obese individuals are
fed hypocaloric diets containing levels of sucrose or high
fructose corn syrup typically consumed by adults in the United
States. SPONSORSHIP: This work was supported by a grant
from the Corn Refiners Association.
Study strengths
The storm of controversy over sugar's role in the obesity
epidemic is still picking up momentum, judging from the major
exposure that researcher/anti-sugar activist Robert Lustig has
received on national television. As mentioned by the authors of
the present study, the American Heart Association has recently
recommended added sugar restrictions that are lower than levels
currently consumed by 90% of adults. Given this, the present
study carries plenty of public health relevance. The prescribed
deficit was moderate (500 kcal), which makes the protocol
realistic for a large segment of the general population. Subjects
received weekly counseling sessions by a registered dietitian
who provided them with menu suggestion & recipes. A formal
exercise protocol was implemented, although it consisted of
walking only (a progression of 15-45 minutes, 3 days per week).
Body composition was assessed via dual X-ray absorptiometry.
Study limitations
The sample size was large, particularly for diet research (247
recruited subjects were divided into 4 experimental groups & 1
control group), but the dropout rate (35%) was high. Although
the authors maintain that this dropout rate is common among
other trials of similar size & duration, it still can negatively
impact statistical power, and it still exceeds typically anticipated
dropout rates, which are roughly 20-30%.8 In trials of a longer
duration, more leeway is given for the acceptability of attrition.
For example, Elobeid et al suggesting that 63% subject retention
(37% dropout) at 12 months was an adequate retention rate in
weight loss trials.9 The authors acknowledge that 78% of the
subjects in the test groups were women, and that elderly subjects
were excluded. The young, female-dominant sample could
potentially be limiting since young women are more resistant to
Alan Aragon’s Research Review – June 2012
the triacylglycerol-raising effects of fructose than men. A final
limitation is that the added sugar was administered within low-
fat milk. As acknowledged by the authors, an increased intake of
vitamin D within the milk could have imparted some protective
effects, such as LDL reduction.
Comment/application
The main finding of this study was a lack of difference in
decreases in bodyweight, body composition, and waist
circumference between the hypocaloric test groups. This study
demonstrated in an elegant fashion that a) sucrose and HFCS are
no different in terms of influencing adiposity, and b) 10-20% of
total kcals as added sugar does not hinder the lowering of blood
lipids (cholesterol & triacylglycerol) typically seen in weight
loss. These results are bound to anger the hordes of sugar-haters.
In terms of absolute numbers, the test groups consumed an
added sugar range of 67.1-95.8 g (HFCS) & 59.1-97.8 (sucrose).
Total carbohydrate intake averaged 246.9 g at baseline and 231.4
at week 12, so there was no significant carb drop throughout the
study. The majority of energy decrease was from a reduced fat
intake. Notably, the latter 2 points reinforce the idea that a
caloric deficit can result in weight (& fat) loss, even when the
targeted reduction isn't carbohydrate-based. While that sounds
elementary to some, there are plenty of folks who actually
believe that carbohydrates prevent fat loss regardless of
imposing a deficit. This is simply not true; in the present case,
clinically significant weight & fat loss occurred in all of the
intervention groups. Interestingly, the 10% HFCS group out-
performed all other conditions in all parameters tested, although
not to a degree of statistical significance compared to the other
hypocaloric treatments. The strongest example of this was body
fat percent change (EO = the exercise-only control group):
Naysayers of this study will inevitably mention that it was
funded by the Corn Refiner's Association. On that basis, many
will dismiss its validity. However, research is best judged on the
merit of its methodology, while still maintaining an awareness of
the potential funding bias. Disregarding results solely due to
funding source is a bias in & of itself. It would be the equivalent
of dismissing all of the omega-3 supplementation studies funded
by the fishing industry, or disregarding all of the low-carb
studies funded by the Atkins Foundation & the beef industry.
[Back to Contents] Page 7

Aspartame in conjunction with carbohydrate reduces
insulin levels during endurance exercise.
Siegler J, et al. J Int Soc Sports Nutr. 2012 Aug 1;9(1):36. [Epub
ahead of print] [Pubmed]
BACKGROUND: As most sport drinks contain some form of
non-nutritive sweetener (e.g. aspartame), and with the variation
in blood glucose regulation and insulin secretion reportedly
associated with aspartame, a further understanding of the effects
on insulin and blood glucose regulation during exercise is
warranted. Therefore, the aim of this preliminary study was to
profile the insulin and blood glucose responses in healthy
individuals after aspartame and carbohydrate ingestion during
rest and exercise. METHODS: Each participant completed four
trials under the same conditions (45 min rest + 60 min self-paced
intense exercise) differing only in their fluid intake: 1)
carbohydrate (2 % maltodextrin and 5 % sucrose (C)); 2) 0.04 %
aspartame with 2 % maltodextrin and 5 % sucrose (CA)); 3)
water (W); and 4) aspartame (0.04 % aspartame with 2 %
maltodextrin (A)). RESULTS: Insulin levels dropped
significantly for CA versus C alone (43 %) between pre-exercise
and 30 min, while W and A insulin levels did not differ between
these time points. CONCLUSION: Aspartame with
carbohydrate significantly lowered insulin levels during exercise
versus carbohydrate alone. SPONSORSHIP: Stephen Atkin
(one of the investigators) provided financial support for the
study.
Author communication during my critique
This is a special study because it's the first one to which
I've formally contributed to its peer-review process. My key
criticisms were as follows, along with the responses from the
authors:
ƒ Me: What was the rationale for not matching the
carbohydrate concentration between the C & CA conditions?
The latter had 2% more carbohydrate, and I feel that this
warrants some explaining.
The authors: Thank you for addressing this inadvertent
omission. It was not our intention to mislead the reviewers,
only a presentation error.
ƒ Me: In the Conclusions section, it's mentioned that
"introducing aspartame as a placebo condition my bias the
results when compared to a carbohydrate ingestion scenario."
I feel that while this might be - at least hypothetically – a
potential concern among those with compromised glucose
control, I'd have to ask why this would be a functional
concern in the healthy population since blood glucose &
exercise performance was unaffected in the subjects of the
present study.
The authors: In this statement, we were attempting to simply
raise the awareness of the potential influence ingesting
aspartame may have on insulinemia. For example, an
investigation looking to compare intracellular signaling
cascades after different feeding strategies pre or post exercise
Alan Aragon’s Research Review – June 2012
may benefit from understanding the influence of using
certain non-nutritive sweeteners as a placebo condition.
However, we do appreciate the reviewers concern with this
statement and in the issue of clarity have removed it.
ƒ Me: In the Background section, it would be helpful to know
what the authors anticipated or hypothesized to happen as a
result of each treatment.
The authors: We have included a hypothesis statement that
hopefully clarifies our anticipated findings. However, due to
the word limitation (1,500) we have not included any further
mention in the Conclusion.
ƒ Me: In the Methods section, it would help to know more
specific details of how the authors define "recreationally
active (e.g., average training days per week, or average hours
of formal exercise per week, etc).
The Authors: We have now included our definition of
recreationally active in the subject description: "…(age: 22 ±
2 years; height: 180 ± 9 cm; weight: 78.6 ± 8.5 kg;
participating in regular physical exercise at least twice per
week)…"
ƒ Me: This paper is missing a Discussion section, in which
speculations can be made about the metabolic effects of
sweeteners other than aspartame, and also some other
ruminations such as why the lack of differences occurred in
all parameters except insulin during exercise.
The authors: Similar to the previous query regarding the
'Findings' subheading, there is not a traditional 'Discussion'
section provided in this format. We appreciate this reviewers
comments regarding additional speculation and
interpretation, however are also conscious of the limited
context available 1,500 word limit for the Short Report
[format]. If the reviewer has further suggestions with regard
to the emphasis of the Conclusion section, we would be
happy to address in a subsequent revision.
ƒ Me: In the Conclusions section, there's no speculation over
why RER was not different between conditions during
training. It seems odd that the W & A (water & aspartame)
treatments would not cause greater fat oxidation during
exercise (& thus present a lower RER). Some speculation as
to why this happened would be helpful.
The Authors: Again due to the word restriction we were
unable to speculate on a number of findings. However, we
believe that the self-selected pace (coupled with the addition
of a monetary incentive (Experimental Protocol) and the
relatively short time frame (e.g. 60 minute) may have
allowed the subjects to overcome the influence of the
nutritional intervention (in a performance context). Perhaps if
the trials were longer duration RER would have illustrated a
greater reliance on FO in the W & A conditions.
ƒ Me: It would be helpful to specify the mean total
carbohydrate intakes (in total grams) of each condition that
contained carbohydrate.
[Back to Contents] Page 8
 The Authors: We have included this information in the
Experimental Protocol section as the following: "…At 15-
minute intervals throughout the trial, subjects were required
to consume 4 ml·kg-1BW of their prescribed drink over a 5-
minute period (total carbohydrate (CHO) consumed during
the trial conditions including CHO was 104.4 ± 11.3 g)…"
ƒ Me: I tend to see the results as more of an opportunity for
athletes to use aspartame-containing drinks as a means to
lower insulin during training & thereby increase lipolysis &
possibly fat oxidation as well. Longer-term trials would
potentially bear out whether or not aspartame is a secret
agent of fat loss reduction due to its effect on insulin levels.
The authors: This is an interesting perspective raised by the
reviewer. The profiling of the insulin response during these
conditions has raised similar questions within our research
team. In future study designs, particularly those in athletic
populations, we will consider measuring (at a minimum)
FFAs.
Study strengths
This study has strong relevance since aspartame is a widely used
sweetener in a range of products consumed by athletes,
including sports beverages. The lab in which the experiments
were done was climate-controlled. The compromised statistical
power of the small sample size was mitigated by the repeated
measures design, all subjects underwent all conditions separated
by wash-out periods of 7-10 days. In order to insure maximal
effort during the exercise trials, a monetary incentive was given
to the subject who accumulated the greatest distance over the 4
trials.
Study limitations
The results of this study might be confined to the 60-minute bout
of self-paced cycling. It's open to speculation whether other
training modes, durations, or intensities would apply.
Furthermore, the results might also be confined to the subjects
used, who weren't necessarily trained athletes; they historically
engaged in physical activity at least twice per week. The amount
of carbohydrate consumed during exercise (~104 g). This was a
rather large amount, considering that a more common amount
consumed for endurance purposes is roughly 60 g per hour
(representing, for example, 1 liter of Gatorade).
Comment/application
The main finding of this study was the significant drop in insulin
levels in the carbohydrate + aspartame condition versus
carbohydrate alone. These findings might have clinical relevance
to those with a compromised insulin action & glucose control,
such as diabetics, whose inherent challenge in predicting the
impact of these factors can yield either hypoglycemia or
hyperglycemia. Marliss & Vranic found that during fasted
exercise at lower intensities, glucose is relatively constant, since
insulin production is inhibited by beta-cell alpha-adrenergic
receptor activation.10 However, this changes in the case of
intense exercise, where glucose production rises 7-8 times fasted
levels, and glucose utilization rises only 3-4 times fasted levels,
leading to a substantial rise in glycemia with only a minimal
Alan Aragon’s Research Review – June 2012
decrease in insulinemia (if at all). In the case of the present
study, lowered insulin levels and heightened glycemia could
spell trouble for those with impaired glucose control. But this is
still merely speculation; an actual study on the effects of
aspartame-sweetened sports beverages on type 1 or type 2
diabetics is yet to be done.
A mysterious outcome in the present study was the lack of
influence on blood sugar levels despite the drop in insulin levels.
The authors suggest that this drop in insulin levels might only be
seen at the threshold of carbohydrate intake, which obviously
was reached in this study. In the carbohydrate-only condition,
blood glucose levels peaked at 20 minutes after the initial
ingestion of the carb-only solution (7 ml/kg). The carb +
aspartame condition caused blood sugar to peak sooner (roughly
10 minutes after ingestion), but the peak was slightly lower.
Note that these phenomena occurred in the pre-exercise period,
where subjects ingested the initial bolus & then waited 45
minutes before the exercise trial. However, it's during training
that things got particularly interesting:
Notice in the above chart, at 30 minutes into the exercise bout,
insulin levels of the carb + aspartame conditions were dropped
to fasted levels, even slightly below the levels in the water
condition. this opens up the possibility that with the addition of
aspartame, fat mobilization (and fat oxidation) can occur to a
greater degree. No significant between-group differences were
seen in respiratory exchange ratio (RER), indicating that
substrate utilization was not differentially affected, despite the
lower insulinemia in the aspartame conditions. It's possible that a
longer exercise duration than 60 minutes would be required for
significant differences to be detected.
As mentioned, an interesting leap of speculation is that
aspartame has the (admittedly remote) potential to increase fat
oxidation during exercise when co-ingested with carbohydrate,
since a reduced insulin production can increase the rate of
lipolysis (fat mobilization). Looking at things optimistically - at
least for non-diabetic populations - lower insulin levels without
lowering glucose availability could result in uncompromised
performance while enhancing fat oxidation. However, a
counterpoint to this idea is that lipolysis is not necessarily
directly representative of fat oxidation. A memorable example of
this is a study by Horowitz et al on moderately trained men
doing either higher-intensity (68% of VO2max) or lower-
intensity exercise (25% of VO2max) in a fed versus fasted
state.11 Despite a suppression of liploysis by 22% in carb-fed
conditions versus a fasted state, no difference in fat oxidation
was seen in the higher-intensity condition, regardless of fed or
fasted training. Nevertheless, it would be cool to see subsequent
incarnations of the present study that measure changes in body
composition and/or glucose control over time.
[Back to Contents] Page 9
 profound. A more ideal design would have included at the very
least, a tracking & reporting of macronutrient intake throughout
The impact of metabolic stress on hormonal the trial - if for nothing else, to see that the subjects were
responses and muscular adaptations. consuming adequate protein for facilitating muscular gains.
Another limitation was the training protocol itself, which began
Goto K, et al. Med Sci Sports Exerc. 2005 Jun;37(6):955-63.
as 3 sets of 3 exercises (lat pull-down, shoulder press, and
[Pubmed]
bilateral knee extension) once per week for the first week,
PURPOSE: The purpose of this study was to examine the progressing to two sessions per week for the following 11
impact of exercise-induced metabolic stress on hormonal weeks. This is a rather low volume of work. Assuming that the
responses and chronic muscular adaptations. METHODS: We subjects were not rank novices, then it's possible that more sets
compared the acute and long-term effects of an "NR regimen" could have enhanced their progress. Petersen et al pooled
(no-rest regimen) and those of a "WR regimen" (regimen with together the findings of 2 meta-analyses and found that
rest period within a set). Twenty-six male subjects were assigned intermediate & advanced trainees maximize their rate of strength
to either the NR (N = 9), WR (N = 9), or control (CON, N = 8) gain at a volume of 4-8 work sets per muscle group per session,
groups. The NR regimen consisted of 3-5 sets of 10 repetitions with 2 sessions per week.6 This is a total weekly volume of 8-16
at 10-repetition maximum (RM) with an interset rest period of 1 sets, which even at the low end is greater than what was used in
min (lat pulldown, shoulder press, and bilateral knee extension). the present study.
In the WR regimen, subjects completed the same protocol as the
NR regimen, but took a 30-s rest period at the midpoint of each Comment/application
set of exercises in order to reduce exercise-induced metabolic
stress. Acute hormonal responses to both regimens were
measured followed by a 12-wk period of resistance training.
RESULTS: Measurements of blood lactate and serum hormone
concentrations after the NR and WR regimens showed that the
NR regimen induced strong lactate, growth hormone (GH),
epinephrine (E), and norepinephrine (NE) responses, whereas
the WR regimen did not. Both regimens failed to cause
significant changes in testosterone. After 12 wk of resistance
training, the NR regimen caused greater increases in 1RM (P <
0.01), maximal isometric strength (P < 0.05), and muscular
endurance (P < 0.05) with knee extension than the WR regimen.
The NR group showed a marked increase (P < 0.01) in muscle
cross-sectional area, whereas the WR and CON groups did
not. CONCLUSION: These results suggest that exercise-
induced metabolic stress is associated with acute GH, E, and NE
responses and chronic muscular adaptations following resistance
training. SPONSORSHIP: The study was supported by grants
from the Ministry of Education, Science, Sports and Culture of
Japan, and from the Research Fellowships of the Japan Society
for the Promotion of Science for Young Scientists.

Study strengths
This study is conceptually strong since it investigated the little-
understood area of potential mechanisms that underlie
hypertrophy & strength gains. This was the first study to ever
examine the effect of interjecting a brief, intra-set rest period
(reducing metabolic stress) on muscular size & strength over a
period of weeks. Training volume & intensity were matched.
Subjects were described as having experience with recreational
resistance training, so it's not like they were newbies or
sedentary folks straight off the couch. Muscle cross-sectional
area (CSA) was assessed via magnetic resonance imaging
(MRI).
Study limitations
A common limitation with training studies is the lack of dietary
control - or in this case, a lack of any mention of diet at all.
It's well-established that diet can influence muscular adaptations
to training over time, so this omission of data is potentially
This study had some highly intriguing outcomes. As seen above,
the no-rest group's body fat percent significantly decreased while
its lean mass significantly increased (Table 1). As for strength
changes, maximal isometric strength and 1-repetition max
(1RM) were superior in the leg extension of the no-rest group
(Table 2). In addition, muscular endurance increase was greatest
in the leg extension performance of the no-rest group, assessed
by exercise volume completed at 70% of 1 RM.
The authors speculate that the no-rest treatment prevailed
because of the greater induction of metabolic stress - which
included higher elevations of growth hormone, epinephrine, and
norepinephrine. In both treatments, there was a lack of

Alan Aragon’s Research Review – June 2012 [Back to Contents] Page 10

significant elevation in testosterone, which the authors mention
is consistent with previous research showing a lack of
testosterone elevation despite ischemia via vascular occlusion.11
The discussion section of the present study touched upon studies
in the mid 1990's that support the authors' hypothesis that greater
metabolic stress can lead to greater training-induced muscular
adaptations. First up, we have Rooney et al, who found that
continuous lifting of a 6-10RM load led to greater strength gains
than the same protocol with 30 seconds of rest between each
repetition.12 The authors speculated that, in addition to neural
factors, the depletion of metaboic fuels or the accumulation of
metabolites such as lactic acid may have been responsible for
these adaptations. The following year, Schott et al compared the
effects of a continuous contraction protocol involving 1-minute
rest intervals between 30-second contractions with an
intermittent contraction protocol involving 2-second rest
intervals between 3-second contractions.13 The continuous
contraction treatment caused greater increases in muscle cross-
section area and intramuscular fatigue metabolites.
This brings us to the discussion of whether or not bodybuilding-
type training (higher reps & shorter rest periods) is indeed more
conducive to hypertrophy than powerlifting-type training (lower
reps & longer rest periods). While the latter is intuitively
conducive to gains in maximal strength, it begs the question of
what makes the former more conducive to muscular size. I
would throw in the caution that the extreme end of high reps &
short rest is not optimal for hypertrophy, since loading capacity
is compromised by the short rest periods. Nevertheless, training-
induced metabolic stress/fatigue - and possibly its accompanying
hormonal flux - might be legitimate contributors to gains in size
and/or strength. Thus, it's likely a good idea to
include/incorporate shorter rest periods and/or higher rep
schemes into programs with the dual objective of size & strength
gains. To quote a recent review by Schoenfeld:14
"Although metabolic stress does not appear to be an essential
component of muscular growth, a large body of evidence shows
that it can have a significant hypertrophic effect, in either a
primary or secondary manner. [...] The stress-induced
mechanisms theorized to mediate the hypertrophic response
include alterations in the hormonal milieu, cell swelling, free-
radical production, and increased activity of growth-oriented
transcription factors. [...] It has also been hypothesized that a
greater acidic environment promoted by glycolytic training may
lead to increased fiber degradation and greater stimulation of
sympathetic nerve activity, thereby mediating an increased
adaptive hypertrophic response."

Alan Aragon’s Research Review – June 2012 [Back to Contents] Page 11

1. Wells FW, Buzby JC: Dietary assessment of major trends in
U.S. food consumption, 1970–2005. In Economic
Information Bulletin No. 33. Economic Research Service,
U.S. Dept. of Agriculture. 2008:1–20.
2. Economic Research Service, USDA. Food Availability (Per
Capita) Data System: Summary Findings. Updated July 5,
2012. [ERS/USDA]
3. Vos MB, et al. Dietary fructose consumption among US
children and adults: the Third National Health and Nutrition
Examination Survey. Medscape J Med. 2008 Jul
9;10(7):160. [Pubmed]
4. Rizkalla SW. Health implications of fructose consumption:
A review of recent data. Nutr Metab (Lond). 2010 Nov
4;7:82.[Pubmed]
5. Beelen M, et al. Protein coingestion stimulates muscle
protein synthesis during resistance-type exercise. Am J
Physiol Endocrinol Metab. 2008 Jul;295(1):E70-7.
[Pubmed]
6. Peterson MD, et al. Applications of the dose-response for
muscular strength development: a review of meta-analytic
efficacy and reliability for designing training prescription. J
Strength Cond Res. 2005 Nov;19(4):950-8. [Pubmed]
7. Staples AW, et al. Carbohydrate does not augment exercise-
induced protein accretion versus protein alone. Med Sci
Sports Exerc. 2011 Jul;43(7):1154-6. [Pubmed]
8. Ahn C, et al. Sample size and power calculations in repeated
measurement analysis. Comput Methods Programs Biomed.
2001 Feb;64(2):121-124. [Pubmed]
9. Elobeid MA, et al. Missing data in randomized clinical trials
for weight loss: scope of the problem, state of the field, and
performance of statistical methods. PLoS One. 2009 Aug
13;4(8):e6624. [Pubmed]
10. Marliss EB, Vranic M.Intense exercise has unique effects on
both insulin release and its roles in glucoregulation:
implications for diabetes. Diabetes. 2002 Feb;51 Suppl
1:S271-83. [Pubmed]
11. Viru M, et al. Effect of restricted blood flow on exercise-
induced hormone changes in healthy men. Eur J Appl
Physiol Occup Physiol. 1998 May;77(6):517-22. [Pubmed]
12. Rooney KJ, et al. Fatigue contributes to the strength training
stimulus. Med Sci Sports Exerc. 1994 Sep;26(9):1160-4.
[Pubmed]
13. Schott J, et al. The role of metabolites in strength training.
II. Short versus long isometric contractions. Eur J Appl
Physiol Occup Physiol. 1995;71(4):337-41. [Pubmed]
14. Schoenfeld BJ. The mechanisms of muscle hypertrophy and
their application to resistance training. Strength Cond Res.
2010 Oct;24(10):2857-72. [Pubmed]

Alan Aragon’s Research Review – June 2012 [Back to Contents] Page 12


John McDougal’s article, “The Paleo Diet Is Uncivilized
(And Unhealthy and Untrue)”
By Alan Aragon
_________________________________________________________________
people off, which admittedly is quite entertaining. Saying that
low-carb diets fuel the destruction of human health is a bold
claim that lacks scientific support. We could just as easily say
the same thing about diets high in refined carbohydrates, and it
would have a stronger research basis. However, it still would be
an incomplete claim. McDougall's labeling of ketosis as a "state
of illness" is not just misleading, but it also isn't supported by
long-term research comparing low-fat & low-carb diets
(including diets that induce ketosis). For the most part, the
literature does not indicate any consistent health-promoting or
disease-preventive advantage to high-carb diets compared to
low-carb diets.2 In fact, in a relatively recent systematic review
of randomized controlled trials, Hession et al concluded that
low-carbohydrate/high-protein diets are more effective for
weight loss than low-fat diets at 6 months, and are as effective, if
not more, as low-fat diets for reducing weight and
cardiovascular disease risk in trials lasting up to 1 year.3

John McDougall, author of The Starch Solution, is a physician
who is perhaps best known for his promotion of a low-fat
vegetarian diet, and also for embarrassing Barry "The Zone"
Sears in a public debate back in 1997. I actually sent for the
audio tape (which I can't play anywhere now since it's an
antiquated cassette). I was impressed with McDougall's prowess
in systematically destroying Sears from several angles, including
a subtle but effective personal shot involving Sears' bodyweight.
Fast-forward to 15 years later, and I happened to stumble upon
an article where McDougall is bashing the Paleo diet,1 with
repeated references to the researcher responsible for giving it
mainstream exposure, Loren Cordain. As many of you know, I
disagree with much of the leaps of logic & faith comprising the
Paleo diet doctrine. I thought it would be interesting to see how a
dedicated tree-hugger like McDougall would rant about it, since
most incarnations of Paleo embrace a copious consumption of
animal foods. My comments will follow McDougall's excerpts
that I feel are relevant. Here's how the article begins (note that
I'm leaving McDougall's embedded links intact):
The Paleo Diet consists mainly of meat, poultry, shellfish, fish, 
and  eggs;  non‐starchy  orange,  green,  and  yellow  vegetables; 
and  fruits  and  nuts.  This  approach  forbids  starches,  including 
all grains, legumes, and potatoes. To its credit it also excludes 
dairy  products  and  refined  sugars.  Salt  and  processed  oils 
(with the exception of olive oil) are also excluded. 
I bolded the clincher above, where MacDougall gives Paleo
credit for kicking out dairy and refined sugar. Hah! It's pretty
hilarious watching a dietary extremist criticize another diet that
in some respects is less extreme. To begin with, complete food
avoidance – regardless of the food – often does more harm than
good. People tend to place a taboo mystique on foods when
they are not on the 'allowed' list. It's as if people become young
children again, and do what it takes to pry open or climb up to
the cookie jar of forbidden goodies instead of learning how to
moderate their intake. The latter skill is much easier when a food
is perceived as morally neutral, rather than good or evil (which
needlessly preys on the emotions and impulses of the dieter).
Teachers  of  Paleo  nutrition  claim  our  ancient  ancestors  were 
hunter‐gathers  with  an  emphasis  on  hunting,  regardless  of 
what the bulk of current scientific research reports. They base 
their hypothesis largely upon a flawed review of contemporary 
hunter‐gathers.  

Low‐carbohydrate  (low‐carb)  diets  are  fueling  the  destruction  McDougall is on-target here. The "flawed review" he's referring
of  human  health  and  our  planet  Earth.  “Low‐carbohydrate”  to is a set of findings by Cordain et al,4 based on the
means a diet high in animal foods and low in plant foods. Only  Ethnographic Atlas, which serves as the basis for many of the
plants  synthesize  carbohydrates  (sugars).  The  body  parts  of  Paleolithic dietary recommendations. McDougall links to a very
animals,  including  red  meat,  poultry,  seafood,  and  fish,  and  memorable & thought-provoking commentary by primate
eggs,  contain  no  carbohydrates.  Animal  secretions  (like  ecologist Katherine Milton.5 The key points she made were as
mammalian  milk)  contain  sugars  synthesized  by  plants  (the  follows:
cow  eats  the  grass  that  made  the  sugar).  The  original  Atkins 
Diet  is  the  ultimate  in  low‐carb  eating.  This  diet  works  by  ƒ The Ethnographic Atlas was compiled largely from 20th
starving the human body of carbohydrates in order to induce a  century sources; some societies coded as hunter-gatherers
state of illness (ketosis), which can result in weight loss. People  like were not exclusively hunter-gatherers or were displaced
become too sick to eat too much.  agricultural peoples.
ƒ The Atlas was compiled by a variety of authors who weren't
Right off the bat, you can tell that McDougall's tone is emotional necessarily interested nor skilled in dietary data collection.
and inflammatory. He appears to be deliberately trying to piss Most ethnographers were male, and since they often did not

Alan Aragon’s Research Review – June 2012 [Back to Contents] Page 13

 associate with women, the larger collection & processing of there's no sound logic in regarding health technology (e.g.,
plant resources by women was likely mis- or underreported. nutrient fortification, supplementation, or the development of
new medicines) as an inherently bad thing. Speaking of
ƒ The final point Milton made is worth quoting directly: cannibalism....
"Finally, all the hunter-gatherers that were included in the
Atlas were modern-day humans with a rich variety of social Archeologists have found bones of our ancestors from a million 
and economic patterns and were not “survivors from the years  ago  with  de‐fleshing  marks  and  evidence  of  bone 
primitive condition of all mankind” (6). Their wide range of smashing to get at the marrow inside; there are signs that the 
dietary behaviors does not fall into one standard victims  also  had  their  brains  eaten.  Children  were  not  off  the 
macronutrient pattern that contemporary humans could menu. And  we are supposed to eat the favorite meats of our 
emulate for better health. Indeed, using data from the same uncivilized,  pre‐Agriculture  Revolution,  hunter‐gather, 
Ethnographic Atlas, Lee (1) found that gathered vegetable ancestors? 
foods were the primary source of subsistence for most of the
hunter-gatherer societies he examined, whereas an emphasis I was going to omit the above passage, since it's a bit redundant
on hunting occurred only in the highest latitudes." after my previous commentary, but then I noticed something
(which I bolded). McDougall is implying that human flesh was a
Paleo  diet  proponents  spare  no  effort  to  ignore  and  distort  "favorite" of our Flintstone ancestors. Although cannibalism
science. The general public is at their mercy until they look for  may have been common among certain societies, I sincerely
themselves  at  recent  publications  from  the  major  scientific  doubt there's any strong evidence that human flesh was a
journals:  predominant source of hedonic consumption in the ancestral
  
population as a whole. This claim seems to be a classic case of
* Research published in the journal Nature (on June 27, 2012) 
sensationalistic journalism on McDougall's part.
reports  that  almost  the  entire  diet  of  our  very  early  human 
ancestors, dating from 2 million years ago, consisted of leaves, 
By nature, the Paleo Diet is based on artery‐clogging saturated 
fruits,  wood,  and  bark—a  diet  similar  to  modern  day 
fats and cholesterol, and bone‐damaging, acidic proteins from 
chimpanzees.  
  animal  foods.  Respected  researchers  find  that  those  modern‐
*  According  to  research  presented  in  a  2009  issue  of  Science,  day  hunter‐gather  populations  who  base  their  diets  on  meat, 
people  living  in  what  is  now  Mozambique,  along  the  eastern  such  as  the  Inuits  (Eskimos),  suffer  from  heart  disease  and 
coast  of  Africa,  may  have  followed  a  diet  based  on  the  cereal  other forms of atherosclerosis, and those modern‐day hunter‐
grass sorghum as long as 105,000 years ago.   gathers who base their diets on plant foods (starches) are free 
 
of  these  diseases.  Osteoporosis,  from  their  high  animal  food‐
*  Research  presented  in  a  2011  issue  of  Proceedings  of  the 
based diets, is also epidemic  among meat and fish consuming 
National  Academy  of  Science  shows  that  even  the 
hunter‐gathers, specifically the Inuits. 
Neanderthals  ate  a  variety  of  plant  foods;  starch  grains  have 
been  found  on  the  teeth  of  their  skeletons  everywhere  from 
the  warm  eastern  Mediterranean  to  chilly  northwestern  If saturated fats and cholesterol were so "artery-clogging," then
Europe. It appears they even cooked, and otherwise prepared,  the research directly comparing animal-fatty diets against low-
plant foods to make them more digestible—44,000 years ago.  fat/low-cholesterol diets would consistently indicate or at least
  suggest this indirectly. But as previously referenced,2,3 this
* A 2010 issue of the Proceedings of the National Academy of  simply has not been the case. For anyone seeking a good read on
Science  reported  that  starch  grains  from  wild  plants  were  this topic, Volk does a fine job of critically reviewing the
identified on grinding tools at archeological sites dating back to  research basis of the anti-saturated fat/anti-cholesterol doctrine
the  Paleolithic  period  in  Italy,  Russia,  and  the  Czech  Republic.  (full text here).6 As for the idea that animal protein's acidic
These  findings  suggest  that  processing  vegetables  and  nature threatens bone health (aside from the fact that the Inuit
starches,  and  possibly  grinding  them  into  flour,  was  a  diet is not the Paleo diet), 3 separate meta-analyses by Fenton et
widespread practice in Europe as far back as 30,000 years ago,  al collectively conclude that urinary calcium does not accurately
or even earlier.   represent calcium balance or actual bone status, and there's
insufficient justification for promoting an alkaline diet for
The above excerpt is a strong collection of research challenging preventing degenerative bone disease.7-9
the idea that grain consumption was an anthropologically recent
phenomenon. This brings up an adjacent fallacy held by Paleo The  June  21,  2012  issue  of  the  British  Medical  Journal 
proponents: the more recent the dietary technology, the further presented the latest updates on the long‐term health hazards 
away it is from our ancestral model, and therefore the worse it is of low‐carbohydrate, high‐protein diets, and reported that, “In 
for our health. This is patently illogical, since our prehistoric particular, women had a 5% higher incidence of cardiovascular 
ancestors had one overriding concern: survival. As such, they ate disease (heart disease) for each tenth of an increase in the low 
whatever was available, and this obviously doesn't automatically carbohydrate‐high  protein  score,  yielding  a  62%  higher 
equate to choosing what's optimal. For example, cannibalism incidence  among  women  in  the  highest  categories  of  low 
during the Paleolithic period, driven by periods of food scarcity carbohydrate‐high  protein  diets  compared  with  the  lowest.” 
as well as cultural ritual, would hardly be regarded as optimal These  low‐carb  diets,  from  Atkins  to  Paleo,  are  simply 
for human health just because our ancestors did it. Ultimately, dangerous. 

Alan Aragon’s Research Review – June 2012 [Back to Contents] Page 14

Linked by McDougall, the recent editorial by Floegel & Pischon References
in the British Medical Journal questions the safety of low-
1. McDougall JA. The Paleo diet is uncivilized (and unhealthy
carb/high-protein diets.10 However, their case is based entirely
and untrue). June 2012. [McDougall Newsletter]
on observational research, which is limited to drawing
2. Hite AH, et al. Low-carbohydrate diet review: shifting the
correlations rather than demonstrating causation. They even
paradigm. Nutr Clin Pract. 2011 Jun;26(3):300-8. [Pubmed]
admit that controlled intervention studies have shown superior
3. Hession M, et al. Systematic review of randomized
therapeutic benefits of low-carbohydrate diets (e.g., reductions
controlled trials of low-carbohydrate vs. low-fat/low-calorie
in triacylglycerol, glycated hemoglobin, insulin, and systolic
diets in the management of obesity and its comorbidities.
blood pressure) compared to low-fat diets. Obes Rev. 2009 Jan;10(1):36-50. [Pubmed]
Furthermore, Floegel & Pischon's concerns are not necessarily 4. Cordain L, et al. Plant-animal subsistence ratios and
relevant to the Paleo diet's most common incarnations. To quote macronutrient energy estimations in worldwide hunter-
them, "A low carbohydrate diet implies low consumption of gatherer diets. Am J Clin Nutr. 2000 Mar;71(3):682-92.
wholegrain foods, fruits, and starchy vegetables and [Pubmed]
consequently reduced intake of fibre, vitamins, and minerals." 5. Milton K. Hunter-gatherer diets-a different perspective. Am
This is simply not descriptive of the popular adaptation of the J Clin Nutr. 2000 Mar;71(3):665-7. [Pubmed]
Paleo diet, which basically adds fruits, vegetables, nuts, and 6. Volk MG. An examination of the evidence supporting the
seeds to the typical Atkins-type diet. This changes its association of dietary cholesterol and saturated fats with
classification to a diet that's not necessarily low-carb or low- serum cholesterol and development of coronary heart
fiber. Therefore, Floegel & Pischon's editorial fails to support disease. Altern Med Rev. 2007 Sep;12(3):228-45. [Pubmed]
McDougall's anti-Paleo position. 7. Fenton TR, et al. Phosphate decreases urine calcium and
increases calcium balance: a meta-analysis of the
The  longest  living  populations  on  planet  Earth  today  live  on  osteoporosis acid-ash diet hypothesis. Nutr J. 2009 Sep
starch‐based  (low‐animal  food)  diets.  These  include  people  15;8:41. [Pubmed]
from Okinawa, Japan; Sardinia, Italy; Nicoya, Costa Rica; Ikaria,  8. Fenton TR, et al. Meta-analysis of the effect of the acid-ash
Greece;  and  the  Seventh  Day  Adventists  in  Loma  Linda,  hypothesis of osteoporosis on calcium balance. J Bone
California, who live in what are called the “Blue Zones.”  Miner Res. 2009 Nov;24(11):1835-40. [Pubmed]
9. Fenton TR, et al. Meta-analysis of the quantity of calcium
The above passage is accurate, and the exceptional health of excretion associated with the net acid excretion of the
Blue Zone populations is a very intriguing area of study. Some modern diet under the acid-ash diet hypothesis. Am J Clin
of it indeed concurs with McDougall's stance. In this regard, Nutr. 2008 Oct;88(4):1159-66. [Pubmed]
review by Appel is worth quoting:11 "Regardless of scientific 10. Floegel A, Pischon T. Low carbohydrate-high protein diets.
approach, there is a remarkable convergence of evidence: BMJ. 2012 Jun 19;344:e3801. doi: 10.1136/bmj.e3801.
Certain aspects of diets improve health and prevent disease, [Pubmed]
particularly CVD." [...] "...dietary patterns associated with 11. Appel LJ. Dietary patterns and longevity: expanding the
longevity emphasize fruits and vegetables and are reduced in blue zones. Circulation. 2008 Jul 15;118(3):214-5.
[Pubmed]
saturated fat, meats, refined grains, sweets, and full-fat dairy
products."
However, unlike McDougall's attachment to low-fat diets, Appel
notes that there's apparently no single-best approach when it
comes to macronutrient composition: "Equally notable is the
wide variation in other aspects of healthy diets, particularly
macronutrient intake. Traditional Okinawan diets provide ≥90%
of calories from carbohydrate (predominantly from vegetables),
whereas the traditional Mediterranean diet provides >40% of
calories from fat, mostly monounsaturated and polyunsaturated
fat."
As tempting as it is to conclude that the diets of Blue Zone
populations are perfect models for achieving optimal health,
correlation does not automatically equal causation. There are a
multitude of factors – both dietary and non-dietary – that
contribute to the longevity of these populations. Therefore, it's
erroneous to assume that longevity and good health cannot be
achieved with a Paleo-type diet that doesn't resemble the starch-
dominant diets in the Blue Zones. And with that, we can
conclude that McDougall is a little over-excited about his
personal dietary ideology, and a little over-reactive & alarmist
toward the Paleo diet. As you can see, zealotry goes both ways.

Alan Aragon’s Research Review – June 2012 [Back to Contents] Page 15

 conditions. In contrast, the higher-carb treatment yielded slightly
more positive nitrogen balance under hypocaloric conditions, but
Carbohydrate is protein-sparing... What exactly does not to a degree of statistical significance. The higher-fat diet also
that mean? resulted in less total weight loss. The authors attributed the
By Alan Aragon greater nitrogen-sparing effect of the higher-fat treatment to its
lower resting energy expenditure (REE) which would
  presumably result in less amino acid oxidation & lower nitrogen
             I always hear people say that carbohydrate is protein‐ 
excretion.
              sparing.    Does  this  mean  that  increasing  carbohydrate 
is better than increasing fat if you want to preserve muscle? 
Tying it together
While there's really no clear-cut winner between carbohydrate
Any nutrient claimed to be "protein-sparing" means that it
and fat for protein-sparing purposes in the existing literature
prevents muscle protein loss (typically measured by nitrogen
(which is scant), it's possible that a higher proportion of
loss, which we now know is a somewhat crude marker). It's
carbohydrate is more protein-sparing in a caloric deficit, while
common to hear that carbohydrates are protein-sparing, perhaps
an equal proportion of carbohydrate and fat is more protein-
due to the simple perpetuation of traditional knowledge. People
sparing at maintenance. Still, all of this data needs to be taken
tend to believe and pass on what's repeated to them enough
with a grain of salt since protein intake levels were less than half
times. In order to assess the validity of this cliché, let's go
of what's typically consumed by athletes and fitness-oriented
through the chronology of research.
folks. Furthermore, none of the aforementioned studies involved
a structured resistance training program.
Beginnings
It's pretty safe to say that dietary protein is more protein-sparing
Perhaps the first study to ever examine the relative effects of
than carbohydrate or fat. It's my hunch that beyond a certain
carbohydrate and fat on protein metabolism was done in 1909 by
protein intake threshold (likely around 2 g/kg or more), the
Cathart, who used himself as the test subject.1 He found that a
nitrogen-retentive differences of varying carb and fat proportion
virtually all-carbohydrate diet caused a decrease in nitrogen loss,
would be negligible. Now, let's be clear that this is not to
while an virtually all-fat diet caused an increase in nitrogen loss.
downplay the importance of sufficient fat for hormonal support
This research had obviously limited real-world applicability, but
and carbohydrate to support progressive training performance.
the more relevant studies took a while to surface. A 1951 review
Both of these factors are crucial for optimizing the increase or
by Munro was in general agreement that although many
retention of muscle mass and strength. Not to mention, different
questions remained, carbohydrates appear to be more protein-
sports and activities have different energy demands - and thus
sparing than fat.2
different carbohydrate requirements.
It wasn't until 1979 that Richardson et al carried out an
When looking at these nutrients in the context of the original
experiment with a fair degree of external applicability.3 Using
question, getting enough protein is the most protective factor,
separate 21-day periods, they compared two conditions: a) an
while the relative muscle protein-sparing effects of carbohydrate
equal ratio of energy from carbohydrate and fat, and b) a 2:1
and fat depends largely on dietary protein sufficiency and state
ratio of carbohydrate to fat – while matching total energy intake
of energy balance.
between conditions. The higher-carbohydrate condition resulted
in less nitrogen loss, but this effect was more consistent in
subjects who lost weight rather than those who gained weight. It References
should also be noted that the subjects' protein intake was set at 1. Cathcart EP. The influence of carbohydrates and fats on
0.57 g/kg, which at the time was considered adequate & in protein metabolism. J Physiol. 1909 Oct 22;39(4):311-30.
accordance with authoritative standards. However, in retrospect, [Pubmed]
this was insufficient for optimizing muscle preservation, 2. Munro HN. Carbohydrate and fat as factors in protein
particularly in hypocaloric conditions. utilization and metabolism. Physiol Rev. 1951
Oct;31(4):449-88. [Pubmed]
A twist in the saga 3. Richardson DP, et al. Quantitative effect of an isoenergetic
In 1989, McCargar et al arrived at contrasting results to the exchange of fat for carbohydrate on dietary protein
previous research.4 Four 14-day conditions were tested. Two utilization in healthy young men. Am J Clin Nutr. 1979
levels of energy balance (maintenance & 75% of maintenance) Nov;32(11):2217-26. [Pubmed]
were tested with two dietary conditions, a 2:1 and 1:1 ratio of 4. McCargar LJ, et al. Dietary carbohydrate-to-fat ratio:
carbohydrate to fat. Protein intake was approximately 1g/kg. influence on whole-body nitrogen retention, substrate
Nitrogen excretion was equal in both diets under hypocaloric utilization, and hormone response in healthy male subjects.
conditions, but under caloric maintenance, the higher- Am J Clin Nutr. 1989 Jun;49(6):1169-78. [Pubmed]
carbohydrate diet yielded a greater nitrogen loss, which was
unexpected given the results of Richardson et al's study.3
Nitrogen balance (intake minus output), which shows a more
complete picture than just nitrogen excretion, was significantly
more positive with the higher-fat treatment under maintenance

Alan Aragon’s Research Review – June 2012 [Back to Contents] Page 16

Here is a fascinating continuum of objects in the universe, which
you can navigate in either direction once it loads.

If you have any questions, comments, suggestions, bones of

contention, cheers, jeers, guest articles you’d like to submit, or
any feedback at all, send it over to aarrsupport@gmail.com.

Alan Aragon’s Research Review – June 2012 [Back to Contents] Page 17